RACIAL VARIABILITY IN GENETIC DETERMINANTS OF BREAST CANCER RISK Almost all studies performed to date have defined breast cancer risk and related genetic profiles in Western European, Caucasian women. We propose a study that will allow us to evaluate the breast cancer-associated genetic profile in young African American women with breast cancer and compare those findings to data from Caucasian women with breast cancer and to a control group we will ascertain for the proposed study. This genetic profile will include not just the high penetrance breast cancer susceptibility genes BRCA1 and BRCA2, but also include a panel of candidate low penetrance risk alleles involved in hormone metabolism. and DNA repair. In addition, we will develop a family history profile of women in both groups to determine whether there are racial differences in the clustering of breast cancer the families of yung women with breast cancer. Finally we will collect a risk factor profile for each participant to evaluate potential confounding variables such as parity, exogenous hormone exposure and smoking history. At the completion of this study, we will defined a genetic profile of this cohort of African American and Caucasian women with regard to breast cancer risk and obtained the data necessary to perform more accurate breast cancer risk assessment in both African American and Caucasian women with regard to breast cancer risk and obtained the data necessary to perform more accurate breast cancer risk assessment in both African American and Caucasian women. As part of the Program Project, we combine the genetic profiling from Project 4 to generate a pharmacogenetic risk model for breast cancer. We also will provide genotyping for a correlative model of response to Tamoxifen, being developed in Projects 1 and 2. At the completion of this project, we will have developed a pharmacogenetic profile that may be used to design the next generation of chemoprevention trials and will add to our understandings of the heritable factors that predict not only breast cancer risk but responsiveness to specific interverions.